Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2012 Oct 9;107(8):1277-85.
doi: 10.1038/bjc.2012.406. Epub 2012 Sep 18.

Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours

M F Kozloff  1 , L P Martin, M Krzakowski, T A Samuel, T A Rado, E Arriola, J De Castro Carpeño, R S Herbst, J Tarazi, S Kim, B Rosbrook, M Tortorici, A J Olszanski, R B Cohen
Affiliations
Clinical Trial

Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours

M F Kozloff et al. Br J Cancer. .

Abstract

Background: This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours.

Methods: In all, 49 patients received axitinib 5 mg twice daily (b.i.d.) with paclitaxel/carboplatin or gemcitabine/cisplatin in 3-week cycles. Following determination of the maximum tolerated dose, a squamous cell NSCLC expansion cohort was enroled and received axitinib 5 mg b.i.d. with paclitaxel/carboplatin.

Results: Two patients experienced dose-limiting toxicities: febrile neutropenia (n=1) in the paclitaxel/carboplatin cohort and fatigue (n=1) in the gemcitabine/cisplatin cohort. Common nonhaematologic treatment-related adverse events were hypertension (36.7%), diarrhoea (34.7%) and fatigue (28.6%). No grade ≥3 haemoptysis occurred among 12 patients with squamous cell NSCLC. The objective response rate was 37.0% for patients receiving axitinib/paclitaxel/carboplatin (n=27) and 23.8% for patients receiving axitinib/gemcitabine/cisplatin (n=21). Pharmacokinetics of axitinib and chemotherapeutic agents were similar when administered alone or in combination.

Conclusion: Axitinib 5 mg b.i.d. may be combined with standard paclitaxel/carboplatin or gemcitabine/cisplatin regimens without evidence of overt drug-drug interactions. Both combinations demonstrated clinical efficacy and were well tolerated.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Treatment schedule for (A) paclitaxel/carboplatin cohorts and (B) gemcitabine/cisplatin cohort. aChemotherapy (CT)=paclitaxel/carboplatin for cohort 1, 2 and 3. C=cycle; Cis=cisplatin; Gem=gemcitabine; PK=pharmacokinetic.
Figure 2
Figure 2
Duration of study treatment.
Figure 3
Figure 3
Plasma concentration–time curves for (A) axitinib, paclitaxel and carboplatin and (B) axitinib, gemcitabine and cisplatin. Abbreviation: PUF=plasma ultrafiltrate.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Berns EM, Klijn JG, Look MP, Grebenchtchikov N, Vossen R, Peters H, Geurts-Moespot A, Portengen H, van Staveren IL, Meijer-van Gelder ME, Bakker B, Sweep FC, Foekens JA (2003) Combined vascular endothelial growth factor and TP53 status predicts poor response to tamoxifen therapy in estrogen receptor-positive advanced breast cancer. Clin Cancer Res 9: 1253–1258 - PubMed
    1. Brown LF, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Dvorak HF, Senger DR (1993) Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am J Pathol 143: 1255–1262 - PMC - PubMed
    1. Burris HA (2009) Shortcomings of current therapies for non-small-cell lung cancer: unmet medical needs. Oncogene 28(Suppl 1): S4–S13 - PubMed
    1. Cohen EE, Rosen LS, Vokes EE, Kies MS, Forastiere AA, Worden FP, Kane MA, Sherman E, Kim S, Bycott P, Tortorici M, Shalinsky DR, Liau KF, Cohen RB (2008) Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol 26: 4708–4713 - PMC - PubMed
    1. Duffull SB, Robinson BA (1997) Clinical pharmacokinetics and dose optimisation of carboplatin. Clin Pharmacokinet 33: 161–183 - PubMed

Publication types

MeSH terms